Successful Live Birth Research Articles

Vitrification alters growth differentiation factor 9 and follicle-stimulating hormone receptor expression in human cumulus-mural granulosa cells.

Ovarian tissue vitrification is widely utilized for fertility preservation in prepubertal and adolescent female patients with cancer. The current literature includes reports of successful pregnancy and live birth following autografting. However, the effects of the vitrification process on cumulus-mural granulosa cells (C-mGCs)-somatic cells in ovarian tissue crucial for oocyte maturation and early embryonic development-remain unclear. This study was conducted to explore the impact of vitrification on the cellular function of C-mGCs by quantifying the expression of growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15), follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), connexin 37, survivin, and caspase 3. Mature and immature C-mGCs were obtained from 38 women with polycystic ovary syndrome who participated in an in vitro fertilization program. The C-mGCs were then divided into two groups: fresh and vitrified. The expression levels of target genes were assessed using real-time quantitative polymerase chain reaction. After vitrification, GDF-9 expression was significantly decreased among both mature and immature C-mGCs, with 0.2- and 0.1-fold changes, respectively (p<0.01). Similarly, FSHR expression in the mature and immature groups was reduced by 0.1- and 0.02-fold, respectively, following vitrification (p<0.01). The expression levels of the other genes, including BMP-15, LHR, connexin 37, survivin, and caspase 3, remained similar across the examined groups (p>0.05). Vitrification may compromise oocyte maturation through reduced GDF-9 and FSHR expression in C-mGCs after warming.

Resistant ovary syndrome: Two case reports and a literature review of effective controlled ovarian stimulation in IVF.

Resistant ovary syndrome (ROS) represents a rare reproductive endocrine disorder that is predominantly associated with infertility, characterized by heightened endogenous gonadotropin levels in the presence of a normal ovarian reserve. Patients with ROS typically exhibit a poor response to exogenous gonadotropins during controlled ovarian stimulation (COS). Due to the absence of a universally accepted effective COS protocol, this study aims to contribute to the existing body of literature by detailing 2 successful pregnancies achieved through conventional in vitro fertilization (c-IVF) in patients with ROS, and through retrospective analysis, seeks to elucidate the factors contributing to the successful ovarian stimulation in these cases, with the ultimate goal of establishing clinical guidelines for ROS management. The central challenge addressed in this study pertains to the effective induction of oocyte maturation during c-IVF COS in ROS patients. The study focuses on 2 infertile women diagnosed with ROS who sought to conceive via c-IVF. The patients were subjected to a COS protocol involving pituitary downregulation followed by ovarian stimulation using recombinant follicle-stimulating hormone (r-FSH) and human menopausal gonadotropin (HMG), preceded by 3 cycles of hormone replacement therapy (HRT) pretreatment. The proposed protocol elicited a favorable ovarian response, culminating in the retrieval of numerous mature oocytes and the development of multiple viable embryos via c-IVF, ultimately leading to successful live births post-embryo transfer. Our study suggests that the outlined COS protocol may serve as a viable treatment option for ROS patients aspiring to conceive through c-IVF, thereby potentially expanding the therapeutic repertoire for this challenging condition.

A new bicornuate model of rat uterus transplantation.

Uterus transplantation has revolutionized reproductive medicine for women with absolute uterine factor infertility, resulting in more than 40 reported successful live births worldwide to date. Small animal models are pivotal to refine this surgical and immunological challenging procedure aiming to enhance safety for both the mother and the child. We established a syngeneic bicornuate uterus transplantation model in young female Lewis rats. All surgical procedures were conducted by an experienced and skilled microsurgeon who organized the learning process into multiple structured steps. Animals underwent meticulous preoperative preparation and postoperative care. Transplant success was monitored by sequential biopsies, monitoring graft viability and documenting histological changes long-term. Bicornuate uterus transplantation were successfully established achieving an over 70% graft survival rate with the passage of time. The bicornuate model demonstrated safety and feasibility, yielding outcomes comparable to the unicornuate model in terms of ischemia times and complications. Longitudinal biopsies were well-tolerated, enabling comprehensive monitoring throughout the study. Our novel bicornuate rat uterus transplantation model provides a distinctive opportunity for sequential biopsies at various intervals after transplantation and, therefore, comprehensive monitoring of graft health, viability, and identification of potential signs of rejection. Furthermore, this model allows for different interventions in each horn for comparative studies without interobserver differences contrary to the established unicornuate model. By closely replicating the clinical setting, this model stands as a valuable tool for ongoing research in the field of uterus transplantation, promoting further innovation and deeper insights into the intricacies of the uterus transplant procedure.

Transplantation and Pregnancy

Transplantation is becoming increasingly widespread worldwide as a life-saving treatment for patients with end-stage organ failure. While the woman's quality of life improves rapidly after transplantation, the improvement of the endocrine system helps to regain fertility. The success of conception and successful pregnancy rates are quite low compared to the general population. Particular attention should be paid to obstetric complications such as hypertension, preeclampsia, fetal growth restriction, and preterm delivery during pregnancy. Ideally, preconception counseling should begin in the period before transplantation. Initiating contraception immediately after transplantation is ideal and long-acting reversible methods such as intrauterine devices and subcutaneous implants may be preferable. Factors that influence pregnancy outcomes in women undergoing organ transplantation include good general health within two years of transplantation, no evidence of organ rejection in the last year, stable graft conditions, absence of acute infections affecting the fetus, and adequate doses of immunosuppression drugs. However, factors that may adversely affect pregnancy include the etiology of the disease requiring transplantation, chronic allograft dysfunction, renal failure, cardiopulmonary diseases, hypertension, diabetes, obesity, and infections such as hepatitis B, hepatitis C, and Cytomegalovirus (CMV). Postponing pregnancy for at least 1 year after transplantation is very important to optimize pregnancy outcomes. Pregnancy in the early post-transplant period increases the risk of acute rejection, infection risk, and graft-related problems. In general, transplanted women can have successful pregnancies and live birth rates are above 70% on average. Although perinatal morbidity and mortality rates are high, most newborns are healthy and develop normally. Specific criteria such as pre-pregnancy serum creatinine levels and blood pressure control, as well as adherence to immunosuppressive therapy, significantly influence pregnancy success in transplant patients. In this review, optimizing pregnancy outcomes often involves addressing maternal and fetal risks, regular graft monitoring to detect potential complications such as organ rejection, and regulation of transplant medications to ensure safety and efficacy during pregnancy. Successful management relies on a multidisciplinary approach with contributions from obstetricians, neonatologists, nephrologists, hepatologists, and transplant surgeons.

Planned oocyte cryopreservation: a systematic review and meta-regression analysis.

Awareness of the age-related decline in fertility potential has increased the popularity of planned oocyte cryopreservation (POC). However, data regarding outcomes of POC, including rates of women returning to thaw oocytes, as well as pregnancy and live birth rates, are scarce and based mostly on small case series. POC was defined as cryopreservation exclusively for prevention of future age-related fertility loss. The primary outcome was live birth rate per patient. The secondary outcomes included the return to thaw rate and laboratory outcomes. A meta-regression analysis examining the association between live birth and age above 40 or below 35 was conducted. We conducted a systematic database search from inception to August 2022. The search included PubMed (MEDLINE) and EMBASE. Our search strategies employed a combination of index terms (Mesh) and free text words to compile relevant concepts. The systematic review and meta-regression were undertaken following registration of systematic review (PROSPERO registration number CRD42022361791) and were reported following guidelines of Preferred Reporting Items for Systematic Review and Meta-Analyses 2020 (PRISMA 2020). The database search yielded 3847 records. After the selection process, 10 studies, conducted from 1999 to 2020, were included. Overall, 8750 women underwent POC, with a mean cryopreservation age of 37.2 (±0.8). Of those, 1517 women returned to use their oocytes with a return rate of 11.1% (± 4.7%). The mean age at the time of cryopreservation for women who returned to use their oocytes was 38.1 (±0.4), with an average of 12.6 (±3.6) cryopreserved oocytes per woman. In a meta-analysis, the oocyte survival rate was 78.5% with a 95% CI of 0.74-0.83 (I2 = 93%). The live birth rate per patient was 28% with a 95% CI of 0.24-0.33 (I2 = 92%). Overall, 447 live births were reported. In a sub-group analysis, women who underwent cryopreservation at age ≥40 achieved a live birth rate per patient of 19% (95% CI 0.13-0.29, I2 = 6%), while women aged ≤35 years old or younger had a higher live birth rate per patient of 52% (95% CI 0.41-0.63, I2 = 7%). POC emerges as a feasible option for women aiming to improve their chances of conceiving at a later reproductive age. Nonetheless, it must be acknowledged that the overall success rates of POC are limited and that the likelihood of successful live birth declines as the age at cryopreservation rises. With increasing interest in POC, the collation of comprehensive and high-quality data is imperative to clearly define the outcomes for various age groups. CRD42022361791.

Clinical outcomes and future fertility after uterine artery embolization for postpartum and post-abortion hemorrhage.

Postpartum hemorrhage (PPH) and post-abortion hemorrhage (PAH) are life-threatening conditions. To evaluate the efficacy and safety of uterine arterial embolization (UAE) for PPH and PAH and to investigate future fertility after UAE. This study included 57 consecutive patients (mean age = 34 years) who underwent UAE for PPH (n = 46) and PAH (n = 11) at our institution between January 2011 and December 2022. Technical success, non-visualization of the peripheral portion of bilateral uterine arteries on angiography, and clinical success, complete hemostasis after UAE, were assessed. UAE-associated complications and factors related to clinical success were analyzed. Pregnancy outcomes after UAE and complications during subsequent pregnancy were investigated in 16 patients who desired fertility and were followed up for >1 year. The technical and clinical success rates were 100% and 84.2%, respectively. Sepsis (n = 1) and uterine empyema (n = 1) were observed as severe complications. Placental disorder, bleeding within 24 h after delivery or abortion, ≥1.5 shock index, ≥6 units of transfusion erythrocytes, and ≥8 obstetrical disseminated intravascular coagulation score were significantly associated with unfavorable clinical outcomes. In total, 16 pregnancies were observed in 12 patients after UAE, three of which were miscarriages and 13 were successful live births. During pregnancy, uterine rupture (n = 1) and accreta (n = 1) were observed. UAE is an effective treatment for PPH and PAH. Although UAE could preserve future fertility, careful attention should be paid to perinatal management for unusual complications.

Dominant depressive, anxious and cyclothymic affective temperaments lower the chance of infertility treatment success

IntroductionAffective temperaments can play a significant role in the development, progression and outcome of various somatic diseases, as well as in the effectiveness of their treatment. Although infertility is influenced by both physical and psychological factors, the relationship between affective temperaments and infertility treatment success remains unexplored.ObjectivesThe aim of this retrospective cohort study was to assess how dominant affective temperaments influence the outcome of infertility treatments.MethodsData was collected from a cohort of infertile women who underwent infertility treatment at an Assisted Reproduction Center in Budapest, Hungary. The study recorded treatment success defined as clinical pregnancy, detailed medical history, demographic parameters, and administered the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). TEMPS-A scores then were classified into nondominant and dominant temperaments for each scale, based on their score being above or below the mean+2 standard deviation for the given temperament. The predictive value of dominant temperaments on assisted reproduction outcomes were analyzed by multivariate logistic regression models, using age, BMI and previous miscarriage as covariates.ResultsIn the cohort of 578 women who underwent infertility treatment, besides age, BMI, and previous miscarriage, dominant depressive, anxious and cyclothymic temperament decreased the odds of achieving clinical pregnancy by 85% (p=0.01), 64% (p=0.03), and 60% (p=0.050), respectively).ConclusionsThe findings of this study suggest that dominant affective temperaments have a significant impact on the outcomes of infertility treatments. As a clinical consequence, creening for affective temperaments, Identifying dominant affective temperaments, stratifying high-risk patient groups, and offering personalized treatment options may enhance the likelihood of successful pregnancy and live birth for women undergoing in vitro fertilization treatment.Disclosure of InterestNone Declared

Assessment of artificial intelligence model and manual morphokinetic annotation system as embryo grading methods for successful live birth prediction: a retrospective monocentric study

PurposeThe introduction of the time-lapse monitoring system (TMS) and the development of predictive algorithms could contribute to the optimal embryos selection for transfer. Therefore, the present study aims at investigating the efficiency of KIDScore and iDAScore systems for blastocyst stage embryos in predicting live birth events.MethodsThe present retrospective study was conducted in a private IVF Unit setting throughout a 10-month period from October 2021 to July 2022, and included the analysis of 429 embryos deriving from 91 IVF/ICSI cycles conducted due to infertility of various etiologies. Embryos incubated at the Embryoscope+ timelapse incubator were analyzed through the established scoring systems: KIDScore and iDAScore®. The main outcome measure was the comparison of the two scoring systems in terms of live birth prediction. Embryos with the higher scores at day 5 (KID5 score/iDA5 score) were transferred or cryopreserved for later use.ResultsEmbryos with high KID5 and iDA5 scores positively correlated with the probability of successful live birth, with KID5 score yielding a higher efficiency in predicting a successful reproductive outcome compared to a proportionally high iDA5 score. KID5 demonstrated conservative performance in successfully predicting live birth compared to iDA5 score, indicating that an efficient prediction can be either provided by a relatively lower KID5 score or a relatively higher iDA5 score.ConclusionThe developed artificial intelligence tools should be implemented in clinical practice in conjunction with the conventional morphological assessment for the conduction of optimized embryo transfer in terms of a successful live birth.

Successful live birth in women with partial 17α-hydroxylase deficiency: report of two cases

RESEARCH QUESTIONCan women with partial 17αhydroxylase deficiency (17-OHD) achieve natural pregnancy with adequate hormonal control and endometrial preparation? DESIGNThis report presents two cases of women with partial 17-OHD who achieved successful pregnancies. The first case involved a 27-year-old Chinese woman with recurrent cysts and infertility, while the second case involved a 32-year-old Chinese woman with complex disorder requiring in vitro fertilization (IVF). Both cases were treated with oral prednisone to control hormone levels and underwent endometrial preparation. RESULTSIn the first case, the patient resumed spontaneous ovulation, conceived naturally, and gave birth to a healthy baby. In the second case, after cryopreserving embryos due to thin endometrium, the patient underwent frozen embryo transfer (FET) and achieved a singleton pregnancy. These cases demonstrate that women with partial 17-OHD can achieve successful pregnancies with adequate hormonal control and endometrial preparation. CONCLUSIONThis report suggests that women with partial 17-OHD can achieve natural pregnancy with appropriate hormonal management and endometrial preparation. These findings provide valuable insights into the reproductive potential of women with this disorder and highlight the importance of further research in this area.

A retrospective cohort study to examine factors affecting live birth following hysteroscopic treatment of intrauterine adhesions

To evaluate independent factors that affect the chance of live birth following hysteroscopic adhesiolysis in patients with intrauterine adhesions (IUAs). Retrospective cohort study SETTING: Hysteroscopic center of Fuxing Hospital in Beijing, China. Patients diagnosed with Asherman syndrome between June, 2020, and February, 2022. Hysteroscopic adhesiolysis followed by second look hysteroscopy to assess outcome and follow-up for a year. Live birth rate without the use of assisted reproductive technologies at 12 months follow-up. (s): Of the 544 women included in the cohort, the pregnancy rate at the end of one year follow-up was 47.6% (95%CI 45.5%-49.7%) and the live birth rate was 41.0% (95%CI 38.9%-43.1%). Stepwise multiple logistic regression analysis identified 3 independent predictors of live birth in decreasing order of significance: increase in menstrual flow after surgery (OR 3.69, 95%CI 1.77-8.21), postoperative endometrial thickness in the mid-luteal phase (OR 1.53, 95%CI 1.31-1.80), and the severity of recurred adhesion at second-look hysteroscopy (OR 0.62, 95%CI 0.50-0.76). Among subjects with good independent prognostic factors, namely, increased menstrual flow after surgery, postoperative endometrial thickness in the mid luteal phase greater than 6mm, no or minimal recurrence of adhesions at second-look hysteroscopy, the live birth rate was 69.0% (95%CI 65.4%-72.6%). On the other hand, in women (n=26) without any of the three good prognostic factors, none had a successful live birth (0%). (s): Overall, the live birth rate following treatment of Asherman syndrome was 41.0%. The prognosis is dependent on three outcome measures following surgery, namely, improvement in menstrual flow, post-operative endometrial thickness and minimal degree of recurrent adhesions at second-look hysteroscopy.

Mosaic embryo transfer versus additional IVF with PGT-A Cycle: a decision model comparing live birth rate and cost.

To evaluate the relative live birth rate and net cost difference between mosaic embryo transfer and an additional cycle of IVF with PGT-A for patients whose only remaining embryos are non-euploid. A decision analytic model was designed with model parameters varying based on discrete age cutoffs (<35, 35-37, 38-39, 40-42, 43-44, >44). Model inputs included probabilities of successful IVF, clinical pregnancy, and live birth as well as costs of IVF with PGT-A, embryo transfer, live birth, amniocentesis, and dilation and curettage. All costs were modeled from the healthcare system perspective and adjusted for inflation to 2023 $USD. Model outcomes were sub-stratified by degree and type of mosaicism. For patients younger than 43, an additional cycle of IVF with PGT-A resulted in a higher relative live birth rate (<35, +20%; 35-37, +15%; 38-39, +17%; 40-42, +6%; average, +14.5%) compared to mosaic embryo transfer with an average additional cost of $16,633. For patients older than 42, mosaic embryo transfer resulted in a higher live birth rate (43-44, +5%; >44, +3%; average, +4%) while on average costing $9572 less than an additional cycle of IVF with PGT-A. Mosaic embryo transfers are a superior alternative to an additional cycle of IVF with PGT-A for patients older than 42 whose only remaining embryos are non-euploid. Mosaic embryo transfers also should be considered for patients younger than 42 who are unable to pursue additional autologous IVF cycles. Counseling and care should be personalized to individual patients and embryos.

A clinical predictive model for live birth in women of advanced age undergoing PGT cycles.

The trend of delaying childbirth has resulted in a growing number of advanced-aged women who are opting for preimplantation genetic testing (PGT) to screen for monogenic diseases or structural chromosomal rearrangements (PGT-M and PGT-SR). This increase in demand necessitates the development of a clinical predictive model for live birth outcomes in these women. Therefore, the objective of this study is to construct a comprehensive predictive model that assesses the likelihood of achieving a successful live birth in advanced-aged women undergoing PGT-M and PGT-SR treatments. A retrospective cohort study of 37-45-year-old women undergoing preimplantation genetic testing for monogenic disease or structural chromosomal rearrangement cycles from 2010 to 2021 was conducted at a university hospital reproductive centre. The purpose was to develop a clinical predictive model for live birth in these women. The main outcome studied was the cumulative live birth rate in the first or subsequent cycles. Developing a decision tree enabled a comprehensive study of clinical parameters and expected outcomes. The analysis included 158 women undergoing 753 preimplantation genetic testing cycles. The cumulative live birth rate was 37.342% (59/158). Decision tree analysis revealed that women aged ≤ 40.1 or women > 40.1 with one or more top-quality transferable embryos in their first cycle had the best chance for a live baby (56% and 41%, respectively). Those older than 40.1 without top-quality embryos and seven or fewer dominant follicles had no live births. A Kaplan-Meier curve showed that for autosomal dominant diseases, there was a negligible increase in live birth rate after three cycles, compared to six cycles in autosomal recessive inheritance. In older women, the chance of delivering after repeated cycles is higher in those with at least one top-quality unaffected embryo in their first preimplantation genetic testing cycle. Additional preimplantation genetic testing cycles after three in carriers of an autosomal dominant disorder and six in those with an autosomal recessive disorder should be considered prudently.

Three live births after human embryo vitrification with the use of aluminum oxide as an intermediate cooling agent: a case report

To study the possibility of increasing the cooling rates of the vitrification procedure in a closed system with the use of aluminum oxide as an intermediate coolant. Case report. Six patients undergoing procedures for assisted reproduction. Comparative studies of cryopreservation of donor embryos with aluminum oxide as an intermediate cooling agent (experimental group) and without it (control group) have been performed. After thawing, the embryo morphology and its potential to develop to the blastocyst stage have been assessed. The methodology was then applied to clinical practice. Twenty embryos of 6 patients have been vitrified on day 4 after fertilization with the use of aluminum oxide as an intermediate coolant. Fourteen of them have been thawed. All have displayed normal morphology and 10 have formed blastocysts after 24 hours of culture. Four of the patients received embryo transfer with 2 embryos and the other 2 with single embryos. After preliminary comparative studies of embryos frozen with aluminum oxide and a control group, the results showed no statistically significant difference between their quality and potential to reach to blastocyst stage. That gave us ground to apply the methodology in clinical practice. After the embryo transfer, 3 clinical pregnancies with successful live births have been obtained. Our experience shows that preimplantation embryos can be cryopreserved aseptically, in closed systems, with the help of aluminum oxide as an intermediate coolant.

Effects of Melatonin, GM-CSF, IGF-1, and LIF in Culture Media on Embryonic Development: Potential Benefits of Individualization.

The implantation of good-quality embryos to the receptive endometrium is essential for successful live birth through in vitro fertilization (IVF). The higher the quality of embryos, the higher the live birth rate per cycle, and so efforts have been made to obtain as many high-quality embryos as possible after fertilization. In addition to an effective controlled ovarian stimulation process to obtain high-quality embryos, the composition of the embryo culture medium in direct contact with embryos in vitro is also important. During embryonic development, under the control of female sex hormones, the fallopian tubes and endometrium create a microenvironment that supplies the nutrients and substances necessary for embryos at each stage. During this process, the development of the embryo is finely regulated by signaling molecules, such as growth factors and cytokines secreted from the epithelial cells of the fallopian tube and uterine endometrium. The development of embryo culture media has continued since the first successful human birth through IVF in 1978. However, there are still limitations to mimicking a microenvironment similar to the reproductive organs of women suitable for embryo development in vitro. Efforts have been made to overcome the harsh in vitro culture environment and obtain high-quality embryos by adding various supplements, such as antioxidants and growth factors, to the embryo culture medium. Recently, there has been an increase in the number of studies on the effect of supplementation in different clinical situations such as old age, recurrent implantation failure (RIF), and unexplained infertility; in addition, anticipation of the potential benefits from individuation is rising. This article reviews the effects of representative supplements in culture media on embryo development.

Affective temperaments show stronger association with infertility treatment success compared to somatic factors, highlighting the role of personality focused interventions

Infertility has a multifactorial background, where, besides somatic factors, psychological contributors also play a role in development and outcome. While affective temperaments have been associated with development, course, and outcome as well as treatment success in various somatic conditions, their association with infertility and its treatment has not been investigated so far. The purpose of our retrospective cohort study was to evaluate the influence of affective temperaments on fertility treatment outcomes. Among 578 women who underwent infertility treatment in an Assisted Reproduction Centre in Budapest, Hungary, treatment success, detailed medical history, and demographic parameters were recorded, and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) was administered. Possible predictors of assisted reproduction outcome were analyzed using multivariate logistic regression models, followed by a receiver operating curve (ROC) analysis in order to define ideal affective temperament cut-off values for clinical applicability. Aside from age, BMI, and previous miscarriage, cyclothymic scores > 4 (OR = 0.51 CI 0.35–0.74, p < 0.001), depressive scores > 9 (OR = 0.59 CI 0.4–0.87, p = 0.009) and anxious scores > 9 (OR = 0.45 CI 0.31–0.66, p < 0.001) significantly decreased the odds of clinical pregnancy by 49%, 41% and 55%, respectively. Irritable and hyperthymic temperaments, as well as other somatic and socio-economic factors had no effect on infertility treatment outcomes. The results suggest that affective temperaments may be related to the outcome of infertility treatments. Thus, screening for affective temperaments may help identify high-risk patient groups and offer patient-tailored treatment, which may increase the chances of a successful pregnancy and live birth for women undergoing IVF treatment.

Does cleavage stage morphology increase the discriminatory power of prediction in blastocyst transfer outcome?

To evaluate the contribution of the cleavage stage morphological parameters to the prediction of blastocyst transfer outcomes. A retrospective study was conducted on 8383 single-blastocyst transfer cycles including 2246 fresh and 6137 vitrified-warmed cycles. XGboost, LASSO, and GLM algorithms were employed to establish models for assessing the predictive value of the cleavage stage morphological parameters in transfer outcomes. Four models were developed using each algorithm: all-in model with or without day 3 morphology and embryo quality-only model with or without day 3 morphology. The live birth rate was 48.04% in the overall cohort. The AUCs of the models with the algorithm of XGboost were 0.83, 0.82, 0.63, and 0.60; with LASSO were 0.66, 0.66, 0.61, and 0.60; and with GLM were 0.66, 0.66, 0.61, and 0.60 respectively. In models 1 and 2, female age, basal FSH, peak E2, endometrial thickness, and female BMI were the top five critical features for predicting live birth; In models 3 and 4, the most crucial factor was blastocyst formation on D5 rather than D6. In model 3, incorporating cleavage stage morphology, including early cleavage, D3 cell number, and fragmentation, was significantly associated with successful live birth. Additionally, the live birth rates for blastocysts derived from on-time, slow, and fast D3 embryos were 49.7%, 39.5%, and 52%, respectively. The value of cleavage stage morphological parameters in predicting the live birth outcome of single blastocyst transfer is limited.

Favorable Fertility Outcome in a Large Cohort of Sickle Cell Disease Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Fertility preservation is an important consideration for individuals with sickle cell disease (SCD) who may face reproductive challenges. While SCD itself does not directly affect fertility, certain complications and its treatment such as hematopoietic cell transplantation (HCT) can impact the reproductive health in SCD patients. HCT is a potential curative therapy for SCD, however, one of the negative outcomes is the premature gonadal failure and infertility. Both male and female patients have different risk factors that may impact the fertility post-transplant. Therefore, these patients should undergo fertility preservation counselling pre transplant. In this study, we report the fertility outcome of large transplant cohort undergoing Non-myeloablative (NMA) conditioning regimen. Methods: We retrospectively collected the data for all SCD patients who were ≥ 14 years old and who underwent allogeneic HCT in our center from 2015 until 2022 with a minimum of 1 year follow up post-transplant. All patients received hydroxyurea for 2 to 3 months pre- transplant at maximum tolerated dose. The conditioning regimen was alemtuzumab 1 mg /kg divided over 5 days from day - 7 to day -3 and Total Body Irradation 200 cGy on day -2 (with testicular shielding for male patients). Graft versus host disease prophylaxis with sirolimus started from day -1 and continued for at least 1 year post-transplant. We started the fertility program in October 2019 where all patients get counselled for fertility preservation methods. Male patients undergo sperm cryopreservation after holding hydroxyurea for 3 months and female patients were referred to a specialized oncology fertility clinic for either oocyte cryopreservation or treatment with Gonadotropin-releasing hormone (GnRH) agonists pre transplant. Primary objective of the study was to assess post-transplant fertility (defined by either ability to conceive for married patients, or development of azoospermia for male patient or secondary amenorrhea for female patients). Secondary objectives were to assess pre transplant fertility, assess the success of different fertility preservations methods and finally to assess for risk factors (pre- transplant and transplant) that affect the fertility potential. Results: We identified a total of 200 SCD patients who underwent HCT. Out of these 200 patients, 107 (54%) were included in our fertility program. The median post-transplant follow up was 3.5 years (1 - 7.5). One hundred and twelve patients (56%) were male, and eighty eight (44%) were female patients. All patients were on hydroxyurea pre transplant with average dose 1000 mg and a duration of less than 2 years in 47 (23.5%) patients, 2 to 5 years in 94 (47%) patients and more than 5 years in 59 (39.5%) patients. Other baseline characteristics are shown in table 1. In the pre-transplant fertility assessment; 58 patients were married and 48 (82%) of them had children pre transplant. 36 male patients attempted sperm cryopreservation and were successful in 33 (91%). 39 female patients received Leuprolide (GNRH agonists) pre-transplant with no complications and 6 female patients attempted oocyte cryopreservation and all were successful. One patient developed cerebral venous thrombosis during the oocyte cryopreservation course. For the post-transplant fertility assessment; out of 57 married patients 26 (45%) were able to conceive. From these 26 pregnancies; 20 ended with successful live-births, 1 ended with abortion and 5 are still pregnant. 6 patients were able to conceive twice and one patient had one twin babies. For male patients 74 did semen analysis at minimum 1 year post-transplant; 35 (47%) had azoospermia and 39 (53%) had viable sperms. Majority recovered spermatogenesis after 1 year (24 patients), at 2 years (9 patients) and after 3 years (3 patients). Three male patients had Azoospermia at one year but was able to conceive successfully without repeating the test. For female patients 71 (80.7%) were able to regain menses and 17 (19.3%) developed secondary amenorrhea. Table 2 shows the pre and post-transplant fertility measures outcome. In conclusion In this study, we have shown the fertility outcomes of male and female patients with SCD undergoing NMA conditioning HCT can be preserved in a significant proportion of patients. All adult patients should be counselled for fertility preservation methods before undergoing curative allogeneic HCT.

Effects of sperm separation methods before intrauterine insemination on pregnancy outcomes and live birth rates: Differences between the swim-up and microfluidic chip techniques.

Various sperm preparation techniques have been developed to obtain functionally, genetically and morphologically high-quality competent spermatozoa for use in assisted reproductive technologies, which may affect treatment options and thus pregnancy outcomes and live birth rates. We aimed to compare swim-up washing procedure (SWP) and microfluidics sperm sorting (MSS) with regard to sperm separation, pregnancy outcomes and live birth rates in infertile couples receiving intrauterine insemination. A total of 326 couples with unexplained infertility who underwent intrauterine insemination were enrolled in this retrospective cohort study and were divided into 2 groups according to sperm preparation technique. The MSS and SWP methods were used to prepare sperm in 178 and 148 patients, respectively. The median sperm concentration reduced significantly from 51 (30-100) million/mL to 20 (10-40) million/mL in the MSS group, and from 45 (26-80) million/mL to 25 (11-48) million/mL in the SWP group (both P < .001). Median motility increased significantly from 30.43 ± 17.79 to 57.48 ± 20.24 in the MSS, and from 32.89 ± 13.92 to 43.91 ± 20.11 in SWP (both P < .001). There was a difference between groups after preparation regarding sperm concentration (better with SWP) and motility (better with MSS) (P = .018 and P < .001, respectively). A total of 86 (26.4%) pregnancies were observed in participants and the clinical pregnancy rate was 23% in the MSS group and 30.4% in the SWP group (P = .133). Fifty-one infants were born alive and a great majority (n = 47) were delivered at term. Multivariate logistic regression analysis showed that higher duration of infertility was independently associated with lower live birth success (odds ratio: 0.811, 95% confidence interval: 0.662-0.996; P = .045). Other variables, including female age, type and reason of infertility, number of cycles, and sperm motility and concentration, were found to be nonsignificant (P > .05). We observed nonsignificant worse reproductive results using microfluid sperm selection in comparison to the pellet swim-up technique (live birth rate = 12% vs 20%). Our evidence is of limited quality due to the retrospective design of this study and sufficiently powered RCTs are needed to evaluate whether sperm selection based using a microfluidic chip is better, similar, or worse than the pellet swim-up technique.

Effect of growth hormone administration on ameliorating pregnancy outcome in women with advanced maternal age and exploration of its optimized utilization.

Age-related fertility decay is a great challenge for clinicians. Growth hormone (GH) supplementation has been studied as an adjuvant since late 1980s. However, it has not come to a consensus on the GH administration due to the ambiguous efficacy among studies with different enrolled population and dosage regime. A self-controlled retrospective study was conducted on women with advanced maternal age who underwent at least a previous cycle without GH (GH-) and a subsequent cycle with GH co-treatment (GH+). The ovarian stimulation parameters and outcomes were compared between the two cycles and logistical analysis was applied to further explore the association between GH administration protocol as well as other clinical parameters and cumulative live birth in GH+cycle. A total of 150 women aged 35-43 were included. The number of oocytes retrieved, MII oocytes, 2PNs, transferrable embryos and good-quality embryos in GH+ significantly increased (p < 0.001). The proportion of cycles with no transferrable embryos was significantly reduced in GH+ cycle compared with previous GH- cycle (3 vs. 32; p < 0.001). GH co-treatment cycles showed significantly higher clinical pregnancy rates (43.75% vs. 6.06%; 38.35% vs. 12.04%, p < 0.001), live birth rates (29.17% vs. 0; 27.07% vs. 0, p < 0.001) in both fresh and frozen-thawed embryo transfer cycle. Cumulative live birth rate of the GH+ cycle reached 33.33%. Use of GH prior to Gn stimulation and lasting until the hCG day seemed to achieve a higher successful live birth rate (OR 2.312, 95%CI 1.074-5.163, p=0.032). GH supplementation could ameliorate pregnancy outcome in women with advanced maternal age. Dosage regimen of long-term pretreatment prior to Gn stimulation (4 IU every other day) and 4 IU per day until hCG day may of greater efficacy compared with concurrent administration with Gn. Additionally, it's worthy of exploring whether an individualized dosage regimen based on the IGF or IGFBP level of patient would be more reasonable and effective. More well-designed prospective trials with large sample size and fundamental experiments on the mechanism are required to testify findings above.

Third-Generation Thyrotropin Receptor Antibody (TRAb) assay for predicting neonatal thyroid dysfunction in pregnant women with Graves' disease.

The aim is to validate the third generation Thyrotropin receptor antibody (TRAb) assay for predicting neonatal thyroid dysfunction and adverse pregnancy outcomes in pregnant women with Graves' disease. This prospective cohort study was conducted in TRAb positive pregnant women with Graves' disease and their off springs. The primary outcome was to assess different forms of neonatal thyroid dysfunction in relation to maternal and neonatal TRAb levels. The secondary outcome was to predict adverse pregnancy outcomes by using maternal TRAb levels. Serum T3, FT4, TSH, TRAb levels were measured using electrochemiluminescence immunoassay. 51 pregnant women were included. Five women had adverse pregnancy outcomes, TRAb levels of > 19.06 IU/L (10.9 times the upper limit of normal (ULN)) predicted adverse pregnancy outcomes with 100% sensitivity and 93.5% specificity. Among the 46 successful live births, 13 (28.3%) had neonatal thyroid dysfunction. Out of 13 neonates, 7 (32%) had neonatal thyrotoxicosis, 4 (18%) had primary hypothyroidism, and 2 (9%) had central hypothyroidism. Third trimester maternal TRAb levels of > 7.99 IU/L (4.6 times the ULN)and day three neonatal TRAb levels of > 5.03 IU/L (2.9 times the ULN), predicted the neonatal thyrotoxicosis with 100% sensitivity and 97.4% specificity. Very high maternal third generation TRAb levels strongly predicted the adverse pregnancy outcomes and neonatal thyroid dysfunction in pregnant women with Graves' disease. Neonatal thyroid function test along with the TRAb levels strongly correlated with different forms of neonatal thyroid dysfunction and is very useful in avoiding inadvertent treatment to neonates.